Photodynamic therapy (PDT) is a methodology used for the treatment of cancer and other ailments. Also sometimes called photochemotherapy, it is a form of phototherapy using nontoxic light-sensitive compounds (photosensitizers) that are exposed selectively to light, whereupon they become toxic to targeted malignant and other diseased cells (phototoxicity). PDT has proven ability to kill microbial cells, including bacteria, fungi and viruses. PDT is popularly used in treating acne. It is used clinically to treat a wide range of medical conditions, including wet age-related macular degeneration and malignant cancers, and is recognised as a treatment strategy which is both minimally invasive and minimally toxic.
Most modern PDT applications involve three key components: a photosensitizer, a light source and tissue oxygen. The combination of these three components leads to the chemical destruction of any tissues which have both selectively taken up the photosensitizer and have been locally exposed to light. The wavelength of the light source needs to be appropriate for exciting the photosensitizer. A number of photo-chemical and/or photo-physical processes are prone to take place when chromophore (i.e. photosensitizer) molecules are promoted to a higher electronic energy or excited state following absorption of the electromagnetic radiation (typically UV or visible light). Among those processes, the excited chromophores may i) transfer their excess energy to an “acceptor” molecule (typically weakly absorbing), e.g. an oxidant such as a peroxide, which in turn may undergo a chemical bond scission to form alkoxyl radicals. The sensitizer may also ii) react directly with other substrates via e.g. electron transfer, forming radical ions. When the above sensitization pathways occur in the presence of oxygen, the previous reactions give rise to Type I photosensitization. The sensitizer may further iii) directly interact with oxygen, either by energy transfer to form singlet oxygen (1O2), or by electron transfer to form superoxide radical anion (O2.−) or hydrogen peroxide (H2O2, a 2 electron process). In the latter case the reaction is referred to as a Type II photosensitization (see FIG. 1).
PDT thus requires for the interaction of light, an active photosensitizer and molecular oxygen. In type II involving formation of singlet oxygen, following excitation of the photosensitizer, rapid intersystem crossing (ISC) takes place from its singlet excited state to the triplet excited state. The triplet excited state next acts as an energy donor to ground state molecular oxygen (3O2) yielding 1O2 generated in situ.
In order to minimize undesired side effects, including damage to healthy tissue during PDT treatment, photosensitization of 1O2 must be controlled at different levels. Conventionally, in order to achieve the selective destruction of the target area using PDT while leaving normal tissues untouched, either the photosensitizer is applied locally to the target area, or photosensitive targets are locally excited with light. For instance, in the treatment of skin conditions, including acne, psoriasis, and also skin cancers, the photosensitizer can be applied topically and locally excited by a light source. In the local treatment of internal tissues and cancers, after photosensitizers have been administered intravenously, light can be delivered to the target area using endoscopes and fiber optic catheters. Thus, the specific targeting of the photosensitizer to ailing over healthy tissue and the precise delivery of the exciting light exclusively to the desired tissue constitute two levels of spatiotemporal control.
Most recently, the chemical activation of a photosensitizer specifically in the targeted tissue has emerged as an effective third level of control. This method exploits differences in the proteome or metabolome of an ailing tissue over the healthy tissue. An enzyme or a chemical agent prevailing in the targeted tissue may site-specifically activate an otherwise dormant chromophore into a potent photosensitizer. Activation/unmasking of the otherwise dormant photosensitizer will occur upon e.g. the enzymatic hydrolysis of the quencher segment.
Photosensitizers can also target many viral and microbial species, including HIV and MRSA. Using PDT, pathogens present in samples of blood and bone marrow can be decontaminated before the samples are used further for transfusions or transplants. PDT can also eradicate a wide variety of pathogens of the skin and of the oral cavities. Given the seriousness that drug resistant pathogens have now become, there is increasing research into PDT as a new antimicrobial therapy.